OPIOID RECEPTOR BLOCKADE THROUGHOUT PRENATAL LIFE CONFERS LONG-TERM INSENSITIVITY TO MORPHINE AND ALTERS MU-OPIOID RECEPTORS

The influence of maternal opioid receptor blockade (50 mg/kg naltrexon e, NTX) or saline (controls) throughout pregnancy on nociception and b rain opioid receptor characteristics of rat offspring were examined; a ll animals were crossfostered to untreated mothers at birth. At 21 and 30 days, NTX-exposed pups weighed 5.2-24.3% more than controls, but b oth NTX and control groups were of similar body weights at 48, 60, and 80 days. Rats in the NTX and control groups displayed comparable base line reactions to the hotplate. Morphine challenge tests and nocicepti ve measures revealed that NTX-subjected offspring examined at 21, 30, 48, and 60 days did not react to dosages that invoked 42-132% decrease s from baseline levers in controls. Animals exposed prenatally to NTX were analgesic when injected with the opioid butorphanol or the nonopi oid xylazine. The binding affinity (K-d) and capacity (B-max) of delta and kappa opioid receptors were similar in NTX and control groups at 21 and 80 days. However, the B-max, but not the K-d, of mu opioid rece ptors was subnormal in NTX offspring by about 20% in contrast to contr ol rats at 21 and 80 days. The results imply that the interactions of some endogenous opioids with opioid receptors during development are d eterminants of certain aspects of pain sensitivity as well as the dens ity of particular opioid receptors in the postnatal period. (C) 1998 E lsevier Science Inc.